, Core C: MHC Genetic Typing Core Genetically well-characterized animal models are critical for the success of HIV/SHIV research, including characterization for MHC genotype, known ancestry, and pedigree relationships. In particular, informative and accurate MHC genotyping is essential, due to the complexity of the MHC class I loci in macaques, and the influence of allele type on disease progression. The need for genetically well-characterized animal models for research must also be balanced against the need to preserve genetic diversity in animal colonies dedicated to supporting biomedical research. This is a requirement not only to ensure long-term colony health, but to ensure the relevance of experimental findings to human disease. The ONPRC is a leader in the development of many of the current recommended approaches and technologies used in genetic typing and management of NHP colonies. Thus, the aims of the Genetics Core for this project are to, 1) use state-of-the-art genetic testing to produce colony offspring of known parentage, ancestry, and MHC genotype and 2) to maintain the genetic diversity of this U42 colony while producing sufficient numbers of offspring to meet research needs. To do this, we will transition parentage analysis in this colony to a new SNP assay based on the Fluidigm platform. We will continue to genotype all new colony offspring for MHC Class I alleles using sequence-based typing, and expand MHC Class I genotyping efforts to include P51 females. We will also conduct genetic management using new protocols developed to assign genetic value for each animal, and to propose breeding groups that will minimize the loss of genetic diversity in the colony. Lastly, we will develop new informatics protocols to support these efforts, including the consideration of MHC type in the maintenance of genetic diversity.
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